Healthy young men were subjected to different degrees of hypoxia at rest and during increased levels of cardiac work induced by atrial pacing and physical exercise at submaximal and maximal loads. Coronary sinus (cs) blood flow was measured by thermodilution and a-cs differences of O2 and lactate were obtained. At low cardiac power output (rest, pacing) the reduction in arterial oxygen content was compensated for mainly by a more complete myocardial oxygen extraction producing lowered cs O2 saturation and tension, while at higher cardiac power (exercise) the compensatory mechanism was entirely an increased coronary blood flow. It was possible to compensate fully for a reduction in arterial O2 saturation of 9% even during maximal physical exercise. With a reduction in arterial oxygen content of more than 20-25% the flow increase was sufficient to supply the heart with enough O2 during submaximal (heart rate 157 beats min-1) but not maximal exercise, in which case anaerobic glycolysis contributed significantly to the myocardial energy metabolism. It is concluded that the normal heart has a 'coronary flow reserve' of about 33% above the flow prevailing during maximal physical exercise under air breathing.

The effect of a reduction in arterial oxygen content, equivalent to acute exposure to an altitude of 2300 metres above sea level, on myocardial blood flow and oxygen and lactate exchange was studied by coronary sinus catheterization in 12 healthy men. Measurements were made at rest, during atrial pacing and during submaximal and maximal exercise both breathing air and breathing 15% oxygen (hypoxia). Coronary sinus blood flow was measured by thermodilution and the possibility of a simultaneous uptake and release of lactate by the heart was calculated using intravenous infusion of 14C lactate. At all levels of cardiac power output myocardial oxygen consumption was the same during hypoxia as during air breathing. At rest this was achieved entirely by a more complete extraction of oxygen from the coronary blood, during maximal exercise entirely by a greater coronary sinus blood flow, while at intermediate levels of cardiac power output a combination of these mechanisms prevailed. At rest and during submaximal work myocardial lactate extraction was lower with hypoxia than air breathing suggesting a change in myocardial redox state, while the 14C lactate data suggested no significant lactate release or possibly limited areas with some lactate production. During maximal exercise, however, there was no difference in myocardial lactate net extraction between hypoxia and air breathing, which together with the greater blood flow suggests that the heart has a 'coronary flow reserve' permitting maximal exercise at moderate altitude without anaerobic myocardial metabolism.

Myocardial O2 delivery and changes in myocardial lactate metabolism during marked hypoxaemia (PaO2 5-5.4 kPa, Sa O2 70-75%) produced by 12% O2 breathing were studied in 12 healthy subjects at rest and during supine exercise up to maximal intensity. Blood for O2 and lactate analyses was sampled from catheters in an artery (a) and the coronary sinus (cs) and coronary sinus blood flow (CSBF) was measured by thermodilution. Lactate metabolism was evaluated in a subgroup of the subjects using i.v. infusion of [14C]lactate. At rest and during submaximal exercise up to heart rate 156 beats min-1 myocardial O2 uptake (MQO2) was maintained at the same level during hypoxaemia as during normoxaemia. This was achieved at rest mainly by a more complete O2 extraction, during exercise entirely by greater CSBF. During maximal exercise CSBF was 35% greater during hypoxaemia than normoxaemia, while there was no difference in cs O2 saturation. Maximal MQO2 was smaller during hypoxaemia than normoxaemia in spite of no difference in rate pressure product. The a-cs difference of lactate was reduced during hypoxaemia and there was a significant myocardial release of lactate, as calculated from [14C]lactate data, during hypoxaemic exercise, but not during hypoxaemic rest or normoxaemic rest and exercise. It is concluded that the heart has a coronary flow reserve of about 35%, which can be utilised under hypoxaemia. When this reserve is insufficient to supply the myocardium with oxygen lactate is produced to cover part of the myocardial ATP regeneration.

To evaluate the effect of hypoxemia on cardiac release of neuropeptide Y-like immunoreactivity (NPY-LI) and norepinephrine (NE), arterial and coronary sinus blood was sampled and coronary sinus blood flow was measured by thermodilution in nine healthy volunteers at rest and during supine cycle ergometer exercise while they breathed air and 12% O2, which reduced arterial O2 saturation to approximately 68%. Five subjects started to exercise for 30 min breathing air and continued for 30 min breathing 12% O2; four subjects breathed 12% O2 and air in the reverse order. The load was adjusted to give the same heart rate during O2 and air breathing. No significant cardiac net release of NPY-LI or NE was seen at rest. Exercise induced release of NPY-LI and NE. The net release of NPY-LI was 0.7 +/- 0.4 pmol/min during air breathing (average 12 and 30 min) and 2.8 +/- 0.6 pmol/min during 12% O2 breathing. The difference was not influenced by the order of the breathing periods. The NE coronary sinus-arterial difference was not significantly different between 12% O2 and air breathing, whereas the net release was significantly larger during 12% O2 breathing (0.6 +/- 0.1 vs. 0.4 +/- 0.1 nmol/min). Thus, NPY is released with NE from the heart during exercise. Arterial hypoxemia seems to be an additional stimulus of preferential NPY release.